These experiments focus on three facets of the hypothalamic- pituitary-adrenal system in the primate (human and rhesus monkey) fetus: 1) the factors responsible for the striking growth of the fetal adrenal gland; 2) the possible functional heterogeneity of fetal pituitary corticotropes and the influence of secretagogues on this heterogeneity; and 3) in vitro and in vivo components of the fetal stress response. Toward this end, an integrated series of in vitro and in vivo studies are proposed. In vitro, the synthesis, regulation, and binding of growth factors and their effects on mitogenic activity in the fetal adrenal will be assessed. In addition, the binding of atrial natriuretic factor to the fetal adrenal and its effect on adrenal steroidogenesis will be determined. Further, the ontogeny and regulation of catecholamines and enkephalins in the fetal adrenal medulla, will be studied. In vivo, the components of the endocrine responses to the specific stresses of hemorrhage, hypoxia and hypotension will be evaluated in the long-term catheterized rhesus fetus in utero. Hormones from the fetal adrenal gland play a key role in the maturation of a variety of enzyme systems necessary for extrauterine life and, in some species, the initiation of labor. Further, the fetus often must react to hemorrhagic and hypoxemic stress at varying times during gestation and labor. In addition, fetal adrenal hormones appear to play a role in surfactant formation essential for lung maturation. Prematurity, with attendant respiratory distress due to lack of lung maturation, is the leading cause of neonatal morbidity and mortality. Therefore, further understanding of the factors regulating the growth and function of the fetal adrenal gland, the neuroendocrine components of the hypothalamic-pituitary-adrenal system, and the involvement of this system in intrauterine fetal homeostasis has significant medical implications.